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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Serie: The Maudsley Prescribing Guidelines Series
- Sprache: Englisch
The Maudsley¯® Deprescribing Guidelines Comprehensive resource describing guidelines for safely reducing or stopping (deprescribing) antidepressants, benzodiazepines, gabapentinoids and z-drugs for patients, including step-by-step guidance for all commonly used medications, covering common pitfalls, troubleshooting, supportive strategies, and more. Most formal guidance on psychiatric medication relates to starting or switching medications with minimal guidance on deprescribing medication. In 2023, the World Health Organisation and the United Nations called for patients, as a human right, to be informed of their right to discontinue treatment and to receive support to do so. The Maudsley Deprescribing Guidelines fills a significant gap in guidance for clinicians by providing comprehensive and authoritative information on this important aspect of treatment. This evidence-based handbook provides an overview of principles to be used in deprescribing. This is derived from fundamental scientific principles and the latest research on this topic, combined with emerging insights from clinical practice (including from patient experts). Building on the recognised brand of The Maudsley Prescribing Guidelines, and the prominence of the authors' work, including in The Lancet Psychiatry on tapering antidepressants (the most read article across all Lancet titles when it was released). The Maudsley Deprescribing Guidelines covers topics such as: * Why and when to deprescribe antidepressants, benzodiazepines, gabapentinoids and z-drugs * Barriers and enablers to deprescribing including physical dependence, social circumstances, and knowledge about the discontinuation process * Distinguishing withdrawal symptoms, such as poor mood, anxiety, insomnia, and a variety of physical symptoms from symptoms of the underlying disorder that medication was intended to treat * The difference between physical dependence and addiction/substance use disorder * Explanation of why and how to implement hyperbolic tapering in clinical practice * Specific guidance on formulations of medication and techniques for making gradual reductions, including using liquid forms of medication, and other approaches * Step-by-step guidance for safely stopping all commonly used antidepressants, benzodiazepines, gabapentinoids and z-drugs, including fast, moderate and slow tapering regimens or schedules for each drug, and guidance on how to tailor these to an individual * Troubleshooting issues which can arise on stopping these medications, including akathisia, withdrawal symptoms, acute or protracted, and relapse. Written for anyone interested in safe deprescribing of psychiatric medications including psychiatrists, GPs, pharmacists, nurses, medical trainees, and interested members of the public. The Maudsley Deprescribing Guidelines is an essential resource on the subject that provides practical guidance on how to improve patient outcomes in this field of medicine.
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Table of Contents
Cover
Table of Contents
Series Page
Title Page
Copyright Page
Preface
Acknowledgements
Notes on using The Maudsley
®
Deprescribing Guidelines
Notes on inclusion of drugs
Contributors’ Conflict of Interest
Abbreviations List
Chapter 1: Introduction to Deprescribing Psychiatric Medications
Deprescribing as an Intervention
The context for deprescribing
Why deprescribe?
Barriers and facilitators to deprescribing
Withdrawal Effects from Psychiatric Medications
Mis‐diagnosis of withdrawal effects as relapse
Pathophysiology of psychiatric drug withdrawal symptoms
Clinical aspects of psychiatric drug withdrawal
Specific issues in psychiatric drug withdrawal
How to Deprescribe Psychiatric Medications Safely
The neurobiology of tapering
Practical options for prescribing gradually tapering doses
Psychological aspects of tapering
Tapering psychiatric drugs in practice
Further topics
Chapter 2: Safe Deprescribing of Antidepressants
When and Why to Stop Antidepressants
Adverse effects of antidepressants
Discussing deprescribing antidepressants with patients
Withdrawal Effects from Antidepressants
Recent developments in the understanding of antidepressant withdrawal
Pathophysiology of antidepressant withdrawal symptoms
Clinical aspects of antidepressant withdrawal
How common, severe and long‐lasting are withdrawal symptoms from antidepressants?
Protracted antidepressant withdrawal syndrome
Post‐SSRI sexual dysfunction
Factors influencing development of withdrawal effects
Stratfiying risk of antidepressant withdrawal
Distinguishing antidepressant withdrawal symptoms from relapse
Distinguishing antidepressant withdrawal symptoms from new onset of a physical or mental health condition
Withdrawal symptoms during antidepressant maintenance treatment or switching medication
How to Deprescribe Antidepressants Safely
Tapering antidepressants gradually
Hyperbolic tapering of antidepressants
Practical options in prescribing gradually tapering doses of antidepressants
Psychological aspects of antidepressant tapering
Tapering antidepressants in practice
Managing complications of antidepressant discontinuation
Tapering Guidance for Specific Antidepressants
Agomelatine
Amitriptyline
Bupropion
Citalopram
Clomipramine
Desvenlafaxine
Dosulepin
Doxepin
Duloxetine
Escitalopram
Fluoxetine
Fluvoxamine
Imipramine
Lofepramine
Mirtazapine
Moclobemide
Nortriptyline
Paroxetine
Phenelzine
Sertraline
Tranylcypromine
Trazodone
Venlafaxine
Vilazodone
Vortioxetine
Chapter 3: Safe Deprescribing of Benzodiazepines and Z‐drugs
When and Why to Stop Benzodiazepines and Z‐drugs
Discussing deprescribing benzodiazepines and z‐drugs
Withdrawal Symptoms from Benzodiazepines and Z‐drugs
Physical dependence vs addiction in use of benzodiazepines and z‐drugs
Pathophysiology of benzodiazepine withdrawal syndrome
Variety of withdrawal symptoms from benzodiazepines and z‐drugs
Protracted benzodiazepine withdrawal syndrome
Distinguishing benzodiazepine withdrawal symptoms from return of an underlying condition
Withdrawal symptoms during benzodiazepine maintenance treatment
How to Deprescribe Benzodiazepines and Z‐drugs Safely
Tapering benzodiazepines and z‐drugs gradually
Hyperbolic tapering of benzodiazepines and z‐drugs
Switching to longer‐acting benzodiazepines to taper
Making up smaller doses of benzodiazepines and z‐drugs practically
Other considerations in tapering benzodiazepines and z‐drugs
Psychological aspects of tapering benzodiazepines and z‐drugs
Tapering benzodiazepines and z‐drugs in practice
Management of complications of benzodiazepine and z‐drug discontinuation
Tapering Guidance for Specific Benzodiazepines and Z‐drugs
Alprazolam
Buspirone
Chlordiazepoxide
Clonazepam
Clorazepate
Diazepam
Estazolam
Eszopiclone
Flurazepam
Lorazepam
Lormetazepam
Nitrazepam
Oxazepam
Quazepam
Temazepam
Triazolam
Zaleplon
Zolpidem
Zopiclone
Chapter 4: Safe Deprescribing of Gabapentinoids
When and Why to Stop Gabapentinoids
Discussing deprescribing gabapentinoids
Overview of Gabapentinoid Withdrawal Effects
Physical dependence vs addiction in use of gabapentinoids
How to Deprescribe Gabapentinoids Safely
Principles for tapering gabapentinoids
Making up smaller doses of gabapentinoids practically
Other considerations in tapering gabapentinoids
Psychological aspects of tapering gabapentinoids
Tapering gabapentinoids in practice
Management of complications of gabapentinoid discontinuation
Tapering Guidance for Specific Gabapentinoids
Gabapentin
Pregabalin
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Barriers and facilitators for patients to stop psychiatric medica...
Table 1.2 Distinguishing features between psychiatric drug withdrawal sympt...
Table 1.3 Potential mis‐diagnoses of drug withdrawal syndromes.
Chapter 2
Table 2.1 Longer‐term use or relapse prevention advice in official guidelin...
Table 2.2 Adverse effects of antidepressants reported by 1,000 patients in ...
Table 2.3 Barriers and facilitators for patients to stop antidepressants....
Table 2.4 Withdrawal symptoms from SSRIs and SNRIs.
*
Table 2.5 Most discriminatory withdrawal symptoms, in order.
14
Table 2.6 Incidence of withdrawal in double‐blind randomised controlled tri...
Table 2.7 The relationship between duration of treatment with an antidepres...
Table 2.8 The relationship between duration of treatment and duration of wi...
Table 2.9 Common antidepressants stratified by risk of withdrawal symptoms,...
Table 2.10 The relationship between dosage of antidepressants and incidence...
Table 2.11 Preliminary tool for evaluation of risk of withdrawal for an ind...
Table 2.12 Estimation of risk category for withdrawal for an individual pat...
Table 2.13 Distinguishing features between antidepressant withdrawal sympto...
Table 2.14 Conditions for which antidepressant withdrawal symptoms are mis‐...
Table 2.15 Trials comparing the effects of different rates of antidepressan...
Table 2.16 Proportion of patients able to discontinue antidepressants in gi...
Table 2.17 SERT occupancy produced by linear reductions of sertraline and t...
Table 2.18 An example reduction schedule for sertraline consisting of 5 per...
Table 2.19 Manufacturer’s liquid and dispersible tablet formulations availa...
Table 2.20 Options available for making up small dosage forms of antidepres...
Table 2.21 Applicability of different options for sertraline, venlafaxine a...
Table 2.22 Estimation of tapering rate based on risk of withdrawal symptoms...
Chapter 3
Table 3.1 Adverse effects of benzodiazepines.
Table 3.2 Barriers and facilitators for patients to stop benzodiazepines an...
Table 3.3 Withdrawal effects from benzodiazepines and z‐drugs, adapted from...
Table 3.4 Most commonly reported symptoms of 1,200 people with protracted wi...
Table 3.5 Benzodiazepine withdrawal symptoms – overlapping with anxiety dis...
Table 3.6 Doses of diazepam required to produce reductions in effect at the ...
Table 3.7 Dose equivalencies between benzodiazepines, their half‐lives and...
Table 3.8 Tablet and liquid formulations available for commonly used benzod...
Chapter 4
Table 4.1 Licensed indications and unlicensed uses for gabapentinoids in th...
Table 4.2 Very common (experienced by more than 10% of participants) and co...
Table 4.3 Typical withdrawal symptoms from gabapentinoids.
1,4,5,9
List of Illustrations
Chapter 1
Figure 1.1 The neurobiology of psychiatric drug withdrawal. In this diagram,...
Figure 1.2 Example of hyperbolic tapering of a psychiatric medication. Dose ...
Figure 1.3 The neurobiology of tapering. In this diagram, the homeostatic ‘s...
Figure 1.4 Linear versus hyperbolic tapering (a) Linear reductions of dose c...
Figure 1.5 An overview of the process of tapering psychiatric drugs. *The de...
Chapter 2
Figure 2.1 Neuro‐adaptation to the presence of antidepressants and the effec...
Figure 2.2 The neurobiology of antidepressant withdrawal. In this diagram, t...
Figure 2.3 The relationship between duration of treatment and proportion of ...
Figure 2.4 Example of hyperbolic tapering of citalopram. Dose reductions are...
Figure 2.5 The neurobiology of tapering. In this diagram, the homeostatic ‘s...
Figure 2.6 (a) Linear reductions of dose cause increasingly large reductions...
Figure 2.7 Hyperbolic pattern of dose reduction produced by tapering strips....
Figure 2.8 Exponential tapering (reducing dose according to a proportion of ...
Figure 2.9 An overview of the process of tapering antidepressants.*What cons...
Figure 2.10 Example monitoring form for a patient reducing from 20mg of cita...
Figure 2.11 Graphical representation of withdrawal symptoms following a dose...
Figure 2.12 Graphical representation of withdrawal symptoms following antide...
Figure 2.13 Graphical representation of withdrawal symptoms following antide...
Figure 2.14 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.15 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.16 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.17 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.18 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.19 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.20 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.21 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.22 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.23 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.24 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.25 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.26 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.27 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.28 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.29 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.30 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.31 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.32 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.33 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.34 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.35 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.36 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.37 (a) Linear reductions of dose cause increasingly large reduction...
Figure 2.38 (a) Linear reductions of dose cause increasingly large reduction...
Chapter 3
Figure 3.1 The difference between the placebo arm and the benzodiazepine arm...
Figure 3.2 The neurobiology of benzodiazepine withdrawal. In this diagram, t...
Figure 3.3 Neuro‐adaptation to the presence of benzodiazepines and the effec...
Figure 3.4 The neurobiology of tapering benzodiazepines. In this figure, the...
Figure 3.5 The effect of linear versus hyperbolic tapering. (a) An example o...
Figure 3.6 An overview of the process of tapering benzodiazepines and z‐drug...
Figure 3.7 Graphical representation of withdrawal symptoms following a dose ...
Figure 3.8 (a) Linear reductions of dose cause increasingly large reductions...
Figure 3.9 (a) Linear reductions of dose cause increasingly larger reduction...
Figure 3.10 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.11 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.12 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.13 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.14 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.15 (a) Linear reductions of eszopiclone. (b) Hyperbolic reductions ...
Figure 3.16 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.17 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.18 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.19 (a) Linear reductions of dose cause slighter larger reductions i...
Figure 3.20 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.21 (a) Linear reductions of dose cause slighter larger reductions i...
Figure 3.22 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.23 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.24 (a) Linear reductions of zaleplon. (b) Hyperbolic reductions are...
Figure 3.25 (a) Linear reductions of dose cause increasingly large reduction...
Figure 3.26 (a) Linear reductions of zopiclone. (b) Hyperbolic reductions ar...
Chapter 4
Figure 4.1 Different approaches to tapering gabapentin. (a) Linear dose redu...
Figure 4.2 Cumulative dose reductions of gabapentin over time in a case stud...
Figure 4.3 An overview of the process of tapering gabapentinoids.*What const...
Figure 4.4 Graphical representation of withdrawal symptoms following a dose ...
Figure 4.5 (a) Linear reductions of dose cause increasingly large reductions...
Figure 4.6 (a) Linear reductions of dose cause increasingly large reductions...
Guide
Cover Page
Table of Contents
Series Page
Title Page
Copyright Page
Preface
Acknowledgements
Notes on using The Maudsley® Deprescribing Guidelines
Abbreviations List
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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The Maudsley Guidelines
Other books in the Maudsley Prescribing Guidelines series include:
The Maudsley Prescribing Guidelines in Psychiatry, 14th EditionDavid M. Taylor, Thomas R. E. Barnes, Allan H. Young
The Maudsley Practice Guidelines for Physical Health Conditions in PsychiatryDavid M. Taylor, Fiona Gaughran, Toby Pillinger
The Maudsley Guidelines on Advanced Prescribing in PsychosisPaul Morrison, David M. Taylor, Phillip McGuire
The Maudsley Prescribing Guidelines for Mental Health Conditions in Physical IllnessSiobhan Gee, David M. Taylor
The Maudsley® Deprescribing Guidelines
Antidepressants, Benzodiazepines, Gabapentinoids and Z‐drugs
Mark Horowitz, BA, BSc(Med), MBBS(Hons), MSc, GDipPsych, PhD
Clinical Research Fellow in Psychiatry and Co‐lead clinician in the Psychotropic Deprescribing Clinic North East London NHS Foundation Trust, Ilford, UK
Honorary Clinical Research Fellow, Department of Psychiatry, University College London, London, UK
David Taylor, PhD, FFRPS, FRPharmS, FRCPEdin, FRCPsych(Hon)
Director of Pharmacy and Pathology
South London and Maudsley NHS Foundation Trust
Professor of Psychopharmacology, King’s College London, London, UK
This edition first published 2024© 2024 John Wiley & Sons Ltd
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Library of Congress Cataloging‐in‐Publication Data Applied forISBN: 9781119822981 (Paperback); 9781119823018 (Adobe PDF); 9781119823025 (EPub)
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Preface
‘It is an art of no little importance to administer medicines properly; but it is an art of much greater and more difficult acquisition to know when to suspend or altogether omit them.’
Philippe Pinel 1745–1826
This is not a book that questions the validity or effectiveness of medicines used for mental health conditions. It is a guide to the deprescribing of psychotropic medication in situations where deprescribing is, on balance, agreed to be a better option than continued prescribing. The agreement here is between prescriber and patient. The core tenet of this text is that decisions are made jointly in the patient’s best interest.
Patients have expressed dissatisfaction – and sometimes outrage – with available medical assistance for stopping psychiatric medications. This has led to many tens of thousands of patients seeking advice from online peer‐support forums. When surveyed, these patients report that their doctors were often unhelpful either because they recommended tapering too quickly or because they were not familiar enough with withdrawal effects to provide helpful advice.1 Some doctors are apparently still suggesting that antidepressants do not cause withdrawal symptoms. The main requests from these patients are that health professionals are sufficiently well informed to provide personalised, flexible reduction plans and that access is provided to smaller doses to facilitate tapering (either liquid versions of medication, or specially compounded smaller dose tablets or capsules).1 We hope this textbook will contribute to a broader understanding of these issues, a greater expertise in helping patients and a better outcome for all.
In writing this textbook we took on what some might consider an impossible task. Safely stopping psychiatric medications is not simply a matter of outlining a regimen of reducing doses for patients to follow. There are too many aspects of the drug, the individual and their lives that come into play such that adjustments inevitably need to be made, often involving a certain amount of trial and error. Yet the most common request we receive from patients and clinicians is to provide tapering schedules to guide reductions. It can be daunting to begin a journey without a map to follow. So in this book we have tried to balance specific guidance with flexibility, offering different routes to reducing doses, whilst trying to accommodate the complexity required for adjusting the course for an individual. We have also tried to acknowledge the tenets of other guidance in this field. The advice given here is, for example, largely consistent with the UK NICE guidelines on this topic, but we aimed to provide greater detail on how to implement the broad principles outlined.
Balancing competing priorities has proved difficult. On the one hand, patients often report that they are tapered off psychiatric drugs too quickly, and on the other, patients should not be exposed for an unnecessarily long time to a drug that could be stopped more quickly. Added to this is the awareness that there is great variation from one person to another – and that we have little to guide us in predicting how an individual will react. We have therefore attempted to accommodate a wide variety of circumstances with further instructions on how to make changes from the suggested regimens.
We wrote this book partly because of our own difficulties in coming off various psychiatric drugs. Our main motivation has been that, by clarifying what is known about safe deprescribing and applying that to practice, we will spare others some of the difficult experiences we have endured. It is perhaps the book that we wished our prescribers had possessed.
It is sobering to consider that had we not experienced stopping medication first‐hand we would have found it hard to believe the accounts of patients, which can seem almost fantastical in the variety and severity of symptoms (what one experienced practitioner in this field has called ‘the unbelievability factor’2). We hope this book will help clinicians develop a greater appreciation for the difficulties some patients experience when trying to stop psychotropic medication.
We recognise that much of the guidance included in this book requires confirmation and clarification from further research but we also appreciate that people are already reducing and stopping their medication and that we should not let the perfect be the enemy of the good. The main messages of the textbook could be summed up in a few words: go slowly, at a rate the patient can tolerate and proceed even more cautiously for the last few milligrams, which are often the hardest to stop.
One major barrier for prescribers we have observed is a reluctance to prescribe liquid versions of drugs, compounded medication or other unlicensed (but widely used) methods to make up the smaller doses of medication necessary for optimal tapering. Often this is for good reasons like cost and complexity. However, minute doses are likely to be required for a substantial proportion of long‐term users if they are to stop their medication safely. Many patients report that once a clinician has traversed this psychological moat the process of tapering off their medication becomes substantially easier.
We have also sought to empower patients in the process of coming off their drugs. Patient autonomy is increasingly highlighted in medicine (and psychiatry more widely), but in the area of deprescribing where relatively little is known and where patient experience is so central, it is even more important. We have observed that patients soon become the experts in understanding what rate they can tolerate in reducing their medications and we hope that clinicians will support patients in this process. An old adage from another area of medicine – ‘Pain is what the patient says it is’ – might be borrowed here. Withdrawal is what the patient says it is.
On this topic, we have also included in this textbook the voices of patient experts and advocates who have been instrumental in drawing attention to the problems many patients face in withdrawal, and in working out innovative approaches to minimise risks. Some of these patient experts have medical training, and some have published research in academic journals. Their experience of being both patients and, in some cases, clinicians brings unique insight into the process.
When discussing withdrawal syndromes from psychiatric drugs, the concepts of addiction or misuse and abuse often arise. However, we have emphasised throughout this textbook that physical dependence is a predictable physiological response to chronic use of psychotropic medication. This inevitably and predictably leads to a withdrawal syndrome on stopping or reducing the dose and does not indicate addiction, misuse or abuse.
This book has been written so that it may be read from cover to cover but it is also designed to be sampled as needed by the busy clinician. To this end, there are ‘quick start’ guides for tapering specific drugs that are designed to be intelligible largely independent of the rest of the book. The chapters on individual drug classes outline the issues specific to each class but also to tapering in general, given some commonalities. This deliberate design has necessitated some degree of repetition, the reasons for which we hope the reader will understand.
We would like to pay special tribute to Adele Framer for sharing the wisdom gained from years of supporting patients to safely stop antidepressants and other psychiatric drugs in peer‐led forums, combining lived experience with academic knowledge. Also, Nicole Lamberson and Christy Huff, medical professionals with lived experience, for contributing their long experience in helping people to safely stop benzodiazepines via peer‐led forums. We would also like to thank Bryan Shapiro for his help putting together the section on gabapentinoids, and Andrea Atri Mizrahi and Ivana Clark for their tireless efforts in assembling and checking for accuracy substantial parts of the drug‐specific guidance. Lastly we would like to record our appreciation for the support of Robin Murray in our work in the field of deprescribing.
Mark Horowitz
David Taylor
London
November 2023
References
1. Read J, Moncrieff J, Horowitz MA. Designing withdrawal support services for antidepressant users: patients’ views on existing services and what they really need.
Journal of Psychiatric Research
2023.
https://www.sciencedirect.com/science/article/pii/S0022395623001309
.
2. Frederick B.
Recovery and Renewal: Your Essential Guide to Overcoming Dependency and Withdrawal from Sleeping Pills, Other 'Benzo' Tranquilisers and Antidepressants
, rev. edn. London: RRW Publishing, 2017.
Acknowledgements
We thank the following for their contributions to The Maudsley® Deprescribing Guidelines
Adele Framer
Alex Macaulay
Andrea Atri Mizrahi
Anna Lembke
Britain Baker
Bryan Shapiro
Christian Müller
Christy Huff
Constantin Volkmann
Daniel Cohrs
Ivana Clark
James Richard O’Neill
Jessica Overton
Laura Nininger Devlin
Louise Bundock
Mary Ita Butler
Michael O’Connor
Nicole Lamberson
Robin Murray
Samuel Bruneau‐Dubuc
Tom Stockmann
Notes on using The Maudsley® Deprescribing Guidelines
The main aim of The Guidelines is to provide clinicians with practically useful advice on the deprescribing of psychotropic agents in commonly encountered clinical situations. The advice contained in this handbook is based on a combination of literature review, clinical experience and expert contribution, including from patient experts and advocates. We do not claim that this advice is necessarily ‘correct’ or that it deserves greater prominence than the guidance provided by other professional bodies or special interest groups. We hope, however, to have provided guidance that helps to assure the safe, effective and economical use of medicines in psychiatry, including when they are no longer required.
We hope also to have made clear precisely the sources of information used to inform the guidance given. Please note that some of the recommendations provided here involve the use of unlicensed formulations of some drugs in order to facilitate tapering. Note also that, while we have endeavoured to make sure all quoted doses are correct, clinicians should always consult statutory texts before prescribing. Users of The Deprescribing Guidelines should also bear in mind that the contents of this handbook are based on information available to us in November 2023. Much of the advice contained here will become out‐dated as more research is conducted and published.
No liability is accepted for any injury, loss or damage, however caused.
Notes on inclusion of drugs
The Deprescribing Guidelines originate in the UK but are intended for use in other countries outside the UK. With this in mind, we have included in this edition those drugs in widespread use throughout the Western world in November 2023. These include drugs not marketed in the UK, such as desvenlafaxine, vilazodone, amongst several others. Many older drugs or those not widely available are either only briefly mentioned or not included on the basis that these drugs were not in widespread use at the time of writing. This book was written to have worldwide utility, although it retains a mild emphasis on UK practice and drugs.
Contributors’ Conflict of Interest
Most of the contributors to The Deprescribing Guidelines have not received funding from pharmaceutical manufacturers for research, consultancy or lectures, although some have. Readers should be aware that these relationships inevitably colour opinions on such matters as drug selection or preference. However, in the case of a textbook that advises on stopping psychiatric drugs, and that generally recommends not using medications to treat withdrawal from another, such conflicts may be less pertinent than in other circumstances. As regards direct influence, no pharmaceutical company has been allowed to view or comment on any drafts or proofs of The Deprescribing Guidelines, and none has made any request for the inclusion or omission of any topic, advice or guidance. To this extent, The Deprescribing Guidelines have been written independent of the pharmaceutical industry.
Abbreviations List
% CI
percentage confidence interval
ADHD
attention deficit hyperactivity disorder
AMPA
α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid
APA
American Psychiatric Association
BDD
body dysmorphic disorder
BIND
benzodiazepine‐induced neurological dysfunction
BNF
British National Formulary
BZD
benzodiazepine
BzRAs
benzodiazepine receptor agonists
CABG
coronary artery bypass graft
CANMAT
Canadian Network for Mood and Anxiety Treatments
CBT
cognitive behavioural therapy
CBT‐I
cognitive behavioural therapy for insomnia
CFS
chronic fatigue syndrome
CNS
central nervous system
COPD
chronic obstructive pulmonary disease
CR
controlled release
CSM
Committee on the Safety of Medicines
DAT
dopamine transporter
DAWSS
Discriminatory Antidepressant Withdrawal Symptom Scale
DESS
discontinuation‐emergent signs and symptoms
DSM‐III‐R
Diagnostic and Statistical Manual of Mental Disorders 3rd revised edition
DSM‐V
Diagnostic and Statistical Manual of Mental Disorders 5th revised edition
EMA
European Medicines Agency
EMPOWER
Eliminating Medications Through Patient Ownership of End Results
ER
extended release
FDA
US Food and Drugs Administration
FND
functional neurological disorder
GABA
gamma‐aminobutyric acid
GABA
A
gamma‐aminobutyric acid type A receptor
GAD
generalised anxiety disorder
GMC
General Medical Council
GP
general practitioner
HAM‐A
Hamilton Anxiety Rating Scale
HAM‐D
Hamilton Depression Rating Scale
HPA
hypothalamic‐pituitary‐adrenal
IBS
irritable bowel syndrome
ICD‐10‐CM
The International Classification of Diseases, 10th Revision, Clinical Modification
IR
immediate‐release
LGIB
lower gastrointestinal bleeds
MADRS
Montgomery‐Åsberg Depression Rating Scale
MAO
monoamine oxidase
MAOI
monoamine oxidase inhibitor
MB‐CT
mindfulness based cognitive therapy
MDD
major depressive disorder
MDMA
3,4‐methylenedioxymethamphetamine
MHRA
Medicines and Healthcare Products Regulatory Agency
MMSE
Mini Mental State Examination
MUS
medically unexplained symptoms
NaSSAs
noradrenaline and specific serotonergic antidepressants
NET
noradrenaline transporter
NEWT
North East Wales NHS Trust
NGO
non‐governmental organisation
NHS
National Health Service
NICE
National Institute for Health and Care Excellence
NIDA
National Institute on Drug Abuse
NMDA
N‐methyl‐D‐aspartate
NNT
number needed to treat
NPS
National Prescribing Service
OCD
obsessive compulsive disorder
ODV
O‐desmethylvenlafaxine
ONS
Office of National Statistics
OR
odds ratio
PAWS
post‐acute withdrawal syndrome
PD
panic disorder
PET
positron‐emission tomography
PIL
patient information leaflet
PPWS
persistent post‐withdrawal syndrome
PSSD
post‐SSRI sexual dysfunction
PTSD
post‐traumatic stress disorder
PWS
persistent withdrawal symptoms
RCPsych
Royal College of Psychiatrists
RCT
randomised controlled trial
RIMA
reversible inhibitor of monoamine oxidase A
RLS
restless leg syndrome
RO
receptor occupancy
RPS
Royal Pharmaceutical Society
SAD
social anxiety disorder
SARI
serotonin antagonist and reuptake inhibitors
SERT
serotonin transporter
SIADH
syndrome of inappropriate secretion of antidiuretic hormone
SMD
standardised mean difference
SmPC
summary of product characteristics
SNRI
serotonin and norepinephrine reuptake inhibitor
SR
sustained‐release
SSRI
selective serotonin reuptake inhibitor
STOPP
Screening Tool of Older Persons’ Prescriptions
TCAs
tricyclic antidepressants
TI
The Therapeutics Initiative
TIA
transient ischaemic attack
UGIB
upper gastrointestinal bleeds
WHO
World Health Organization
XR or XL
extended‐release
Z‐drugs
nonbenzodiazepine sedative‐hypnotics
Chapter 1Introduction to Deprescribing Psychiatric Medications
Deprescribing as an Intervention
Deprescribing is the planned and supervised process of reducing or stopping medication for which existing or potential harms outweigh existing or potential benefits.1 The term ‘deprescribing’ originates from geriatric medicine where polypharmacy in frail patients can cause more harm than benefit.1 Deprescribing is increasingly recognised to be a key component of good prescribing – reducing doses when they are too high, and stopping medications when they are no longer needed.2 This process cannot occur in a vacuum of theoretical concerns but should take into account the patient’s health, current level of functioning and, importantly, their values and preferences.1 Deprescribing seeks to apply best practice in prescribing to the process of stopping a medication. It requires the same skill and experience as for the process of prescribing from prescribers, as well as support from pharmacists and other healthcare staff to obtain the best results. Importantly, it should place patients at the centre of the process to ensure medicines optimisation.3
There has historically been little attention paid to deprescribing in psychiatry. There is a dearth of research into a structured approach to stopping psychiatric medication, with the exception of some early studies examining stopping benzodiazepines1 and in some specific populations, like people with learning disabilities. The focus of research efforts has been predominantly the prescribing of psychiatric medications – for example, there are estimated to be about 1,000 (published and unpublished) studies on starting antidepressants and only 20 on stopping them.4 Concern about this imbalance is not specific to psychiatry with other medical specialties, such as cardiology, also engaging in a re‐appraisal of long‐term medication continuation, with support for developing strategies for repeated risk–benefit analyses over time.5
The context for deprescribing
Over‐prescription in psychiatry
Despite evidence of benefit for psychiatric drug treatment, there have been concerns raised regarding over‐prescription. 1 in 6 people in western countries are prescribed an antidepressant in any given year, with rates rising a few per cent each year.4,6 These increasing prescription numbers are mostly caused by longer periods of prescribing – the median duration of use of antidepressants is now more than 2 years in the UK and more than 5 years in the USA.6 Some commentators have suggested that the increasing duration of prescriptions in part reflect the difficulty people have in stopping these medications due to withdrawal effects.7 In practice, 30–50% of patients do not have evidence‐based reasons for the continued prescription of antidepressants,8–10 prompting calls to action to reduce associated risks.6,11 There have been similar concerns about the high rates of antipsychotic use in conditions other than serious mental illness,12 as well as a reconsideration of their open‐ended use in psychotic conditions for all patients.13,14 There are long‐standing worries about levels of benzodiazepine and z‐drug prescribing,15,16 and more recent concerns about gabapentinoid prescribing.17
High rates of medication prescribing has also gained governmental attention in the UK,17 with a particular focus on psychiatric drugs. A government report has noted that 1 in 4 adults in the UK are prescribed at least one dependence forming medication each year, with some patients having difficulties stopping these medications.18 One central concern is that short‐term symptom control might be prioritised over long‐term functional outcomes, especially as most studies guiding treatment protocols measure symptomatic outcomes over short time periods rather than functional outcomes (or other outcomes often valued by patients) over longer time periods.13,19,20
Alongside this disquiet regarding over‐prescription there has been renewed scrutiny of the effectiveness of some psychiatric medications. There is some consensus in the UK and Europe that benzodiazepines and z‐drugs have limited effectiveness in the long term, with guidance recommending against long‐term treatment for anxiety and insomnia,21 matched by guidance in the USA from some health management organisations.15 Preliminary studies have recently found similar outcomes in the treatment of selected patients with first‐episode psychosis with or without antipsychotics in the context of comprehensive psychosocial support,22,23 and non‐drug treatment for serious mental illness has attracted increasing interest, including a large randomised controlled trial (RCT).24 There have been calls from clinicians and patients for ‘minimal medication’ options for the treatment of psychotic conditions, such as have been established in Norway and parts of the USA.25 There has continued to be debate regarding the efficacy of antidepressants26,27 with arguments being made for their use in selected populations.28 Concerns have emerged regarding the efficacy and safety of gabapentinoids.17 In some countries there has been a shift away from a drug‐centric approach in some patient groups – for example, in England and Wales the National Institute for Health and Care Excellence (NICE) now recommends that mild depression should not be treated with antidepressants as a first‐line treatment, and suggests eight equally effective (and cost‐effective) non‐pharmacological treatment options for severe depression, alongside medication options.29
In addition to the above, there has also been significant critical attention directed towards the relapse prevention properties of psychiatric drugs.30,31 All psychiatric drug classes are recognised to cause withdrawal effects when stopped that may be misinterpreted as relapse of the initial condition necessitating treatment.32 These withdrawal symptoms are often ignored in discontinuation studies examining relapse prevention properties.30,33,34 As a result there have been questions raised as to whether the relapse prevention properties of psychiatric drugs have been over‐stated by mis‐classification of withdrawal effects as relapse,30,33,34 indicating we should be cautious in our interpretation of these studies.
Research and guideline establishment in deprescribing
In recent years interest in psychiatric deprescribing has increased exponentially. Numerous studies have been conducted or are ongoing exploring reducing and stopping antipsychotics in first and multi‐episode psychotic conditions, in Taiwan, France, Denmark, the Netherlands, England, Australia and Germany, including the establishment of an international research consortium.14 Some of these studies are examining gradual reductions, or hyperbolic dose reductions specifically.14,35 Alongside this there are studies looking at how to help patients stop antidepressants – in the UK,36 the Netherlands37 and in Australia38 – as well as several published studies looking at substitutions for antidepressant treatment like preventative cognitive therapy or mindfulness‐based cognitive therapy.39–41
There has been increasing interest in the process of stopping medication based on the pharmacological properties of the drugs,42–45 as well as in the practical means for making gradual dose reduction (for example, using compounded tablets in very small doses).46–48 There has also been increased focus on the non‐pharmacological aspects of reducing and stopping medication – the positive and negative impact on people’s lives, as well as the barriers and the facilitators.1,49–52
In parallel, there has been increasing institutional interest in deprescribing in some countries. In the UK, in recent years, there has been guidance issued by the Royal College of Psychiatrists on how to safely stop antidepressants,53 as well as guidance from NICE on how to stop antidepressants, benzodiazepines, z‐drugs, opioids and gabapentinoids.54 Similar guidance on how to stop antipsychotics has been called for.55 In England, the National Health Service (NHS) has introduced structured medication reviews to reduce the use of unnecessary medication, including some psychiatric drugs,56 and the Department of Health and Social Care has been tasked with upscaling deprescribing capacity in the NHS.18
Many clinicians report an interest in deprescribing and in receiving training for its practice. In total, 75% of UK clinicians working in first‐episode psychosis services thought that early discontinuation of antipsychotic medication was beneficial for most patients.57 In patients with multiple psychotic episodes English psychiatrists reported that they would feel comfortable supporting about 20% of their patients to discontinue their antipsychotics, with a minority of psychiatrists comfortable to support greater proportions.58 In a survey 68% of GPs expressed a desire for more training on the withdrawal effects of antidepressants.59 As mentioned, in Norway, government directives have led to the establishment of ‘drug‐free’ wards, in which deprescribing is a central activity.25 There are several dedicated psychiatric drug deprescribing services established around the world situated either in public or private healthcare settings or run by NGOs partnered with health systems.60 Indeed, several academics and psychiatrists have written about their own experience stopping psychiatric medication, often with the theme that this process was far more difficult than the published literature or their training had intimated.61–63
Patient knowledge and advocacy
This rise in academic, professional and institutional interest in psychiatric drug deprescribing has lagged behind decades of interest in the topic by patient groups who have sought ways to rationalise (and generally reduce) their medication in the relative absence of professional help. This movement seems driven by the subjectively unpleasant effects and physical health consequences from being on such medications.64–67 It is noteworthy that much of the academic work now being conducted in deprescribing borrows from the expertise developed by patient groups.44,48,62,66 Groups of patients (often supported by clinicians) have created guidance and advice on the topic of deprescribing in various guides and websites.64,66,68 Manuals like The Ashton Manual (written by the clinical pharmacologist Professor Heather Ashton) are widely used in peer‐led withdrawal communities,69 and this manual has influenced NICE guidance on withdrawing from benzodiazepines.70 Alongside this there has been substantial patient advocacy for more clinical services for deprescribing, which has been part of the driving force in the shift of interest to this topic,64,71–73 as well as increasing media attention to the issue of how to safely stop psychiatric medications and the adverse consequences of stopping too rapidly.74–78
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Why deprescribe?
A variety of clinical scenarios may warrant deprescribing. These include:
high‐dose prescribing,
polypharmacy (drug‐drug interactions, effects on adherence, and medical risk in vulnerable populations).
inappropriate prescribing (wrong drug, dose or duration),
patient preference,
harms outweighing benefits,
condition improved, resolution of stressors or alternative coping strategies developed.
High‐dose prescribing, polypharmacy, inappropriate prescribing
It is widely agreed that high‐dose prescribing and polypharmacy can, in many instances, produce more harm than benefit.1 For many psychiatric conditions, including major depressive disorder, there is no clear advantage to high‐dose pharmacotherapy, although the risks of adverse effects can increase as a function of dose.2 The lower range of licensed doses is thought to achieve an optimal balance between efficacy, tolerability and acceptability in acute treatment.2 The potential harms of high‐dose antipsychotic prescribing and psychiatric drug polypharmacy are also well recognised.1 Additionally, potentially inappropriate prescribing of psychiatric medication occurs commonly – including chronic polypharmacy for patients with personality disorders, in which guidance generally recommends avoiding pharmacological treatment or employing it for short‐term use.3
